1. Field of the Invention
The present invention is related to methods for performing radiation therapy for cancer treatment. More particularly, the invention relates to methods of using arrays of small radiation beams to irradiate tumors.
2. Background of the Related Art
Cancer continues to be one of the foremost health problems. Conventional treatments such as surgery and chemotherapy have been extremely successful in certain cases; in other instances, much less so. Radiation therapy has also exhibited favorable results in many cases, while failing to be completely satisfactory and effective in all instances. A much less familiar alternative form of radiation therapy, known as microbeam radiation therapy (MRT), is being investigated to treat certain tumors for which the conventional methods have been ineffective.
MRT differs from conventional radiation therapy by employing beams of radiation that are one order of magnitude smaller in diameter than the smallest radiation beams currently in clinical use. The diameter of the microbeams is dependent upon the capacity of tissue surrounding a beam path to support the recovery of the tissue injured by the beam. It has been found that certain types of cells, notably endothelial cells lining blood vessels, have the capacity to migrate over microscopic distances, infiltrating tissue damaged by radiation and reducing tissue necrosis in the beam path. In MRT, sufficient unirradiated or minimally irradiated microscopic zones remain in the normal tissue, through which the microbeams pass, to allow efficient repair of irradiation-damaged tissue. As a result, MRT is fundamentally different from other forms of radiation therapy.
In conventional forms of radiation therapy, including the radiosurgical techniques employing multiple convergent beams of gamma radiation described by Larsson "Potentialities of Synchrotron Radiation in Experimental and Clinical Radiation Surgery, " Acta Radiol Ther. Ph. Biol. Suppl., 365, 58-64 (1983), each beam is at least several millimeters in diameter, so that the biological advantage of rapid repair by migrating or proliferating endothelial cells is minimal or nonexistent. As described in greater detail below, our observations of the regeneration of blood vessels following MRT indicate that endothelial cells cannot efficiently regenerate damaged blood vessels over distances on the order of thousands of micrometers (.mu.m). Thus, in view of this knowledge concerning radiation pathology of normal blood vessels, the skilled artisan would optimally select microbeams as small as 50 .mu.m to 200 .mu.m in diameter.
The division of a radiation beam into microbeams, and the use of a patient exposure plan that provides non-overlapping beams in the tissue surrounding the target tumor. This allows the non-target tissue to recover from the radiation injury by migration of regenerating endothelial cells of the small blood vessels to the areas in which the endothelial cells have been injured beyond recovery. Therefore, the probability of radiation-induced coagulative necrosis in normal, non-targeted tissue is lowered, which should improve the effectiveness of clinical radiation therapy for deep-seated tumors. The use of microbeams should be of special benefit for deep pulmonary, bronchial, and esophageal tumors, for example, where the effectiveness of orthodox radiation therapy is limited by the risk of radiation pneumonitis.
Effects on the mouse brain of 22 MeV deuterons delivered in a beam having either a circular cross-section (herein designated a "cylindrical" beam) 25 .mu.m in diameter or an elongated rectangular cross-section (herein designated a "planar" beam) 25 .mu.m in width were investigated 3 decades ago. Representative investigations are described by Ordy et al., "Long-Term Pathologic and Behavioral Changes in Mice After Focal Deuteron Irradiation of the Brain", Radiation Research 20, 30-42 (1963). The Ordy et al. publication describes the effects of exposure to high energy deuteron microbeams having a 9 mm .times.0.025 mm planar configuration. These beams of heavy charged particles were used in experiments to model the neurological effects of extraterrestrial heavy ions on humans. Ordy et al. do not discuss the treatment of tumors by X-ray microbeam irradiation.
Damage to the cerebrum and cerebellum caused by the deuteron microbeam, was not evident unless a very high radiation dose was given. A macroscopic (1 mm diameter) 22 MeV deuteron beam that delivered about 150-300 Gray (Gy) to the mouse cerebrum caused tissue necrosis in its path. On the other hand, energies of at least 3000 Gy to the cerebral cortex or 720 Gy to the cerebellar cortex were required to leave any persistent brain damage in the path of a 22 MeV, 25- to 40-.mu.m-wide cylindrical or planar deuteron microbeam, as observed by light microscopy up to 9 months after irradiation. Furthermore, damage was limited to cellular necrosis. Tissue necrosis in the microbeam-damaged zone of the mouse brain was apparently averted by regeneration of blood vessels, even after an absorbed dose of 10,000 Gy or more in the path of the microbeam. Any vascular or parenchymal cell in the microbeam that had been so intensely irradiated was probably destroyed. Cellular necrosis caused by the deuteron microbeam depended mainly on the absorbed dose rather than on the absorbed dose rate, which was varied from 2 to 9,000 Gy s.sup.-1.
These unprecedented dose-effect relationships in the brain were attributed to the narrowness of the beams and to the regeneration of blood vessels in tissues within the path of the microbeam from the microscopically contiguous, minimally irradiated vasculature adjacent to that path. Presumably, minimally irradiated blood vessels contained reservoirs of endothelium from which regenerating endothelial cells grew into the nearby, maximally irradiated blood vessel segments as the endothelial cells of the latter segments died and disintegrated.
A microbeam tissue-sparing effect was also observed for X-ray microbeams by Straile and Chase, in "The Use of Elongate Microbeams of X-Rays for Simulating the Effects of Cosmic Rays on Tissues: A Study of Wound Healing and Hair Follicle Regeneration", Radiation Research, 18, 65-75 (1963). This publication describes the irradiation of mouse skin using a 200 kVp, 0.5 mm Cu+1.0 mm Al-filtered X-ray source. Absorbed doses of about 60 Gy produced a variety of skin lesions when delivered in a seamless (i.e., not spatially interrupted) 5 mm diameter beam. However, much less severe damage occurred when similar doses were delivered to the skin via a 150 .mu.m wide microbeam. These investigators were primarily concerned with modelling the effects of cosmic rays, and did not describe or suggest the use of microbeams for any therapeutic purposes.
A publication by L. Leksell, "The Sterotaxic Method and Radiosurgery of the Brain, " Acta Chirugica Scandinavia, 102, 316-319 (1951), describes a stereotaxic instrument suitable for cross-firing radiation treatment of brain tumors. The Leksell publication does not describe the use of microbeams or of multiple simultaneous beams. A related publication by B. Larsson entitled "Potentialities of Synchrotron Radiation in Experimental and Clinical Radiation Surgery," Acta Radiol. Ther. Ph. Bios. Suppl., 365, 58-64 (1983), which further describes the stereotaxic method of Leksell. In addition, Larsson describes a hemispherical helmet-like apparatus for gamma radiation of intracranial targets by multiple converging channels. Larsson does not, however, discuss microbeams or any method of producing microbeams.
U.S. Pat. No. 2,638,554 to Bartow et al. describes various collimators for X-rays which produce a conically converging array of very small beams. One of the collimators described by Bartow et al. is a truncated cone of X-ray-impermeable material cast around a removable array of wires. Once the wires are removed, an array of apertures remains in the collimator which, when inserted into a beam of X-rays, will produce a convergent array of very small beams. The apertures are described as being in the range of 0.25 inches (6.4 mm) to 0.001 inches (25.6 .mu.m). Another lens described by Bartow et al. is an arcuate lens assembled from planar segments into which grooves have been cut so that when assembled each of the isofocused grooves defines an X-ray transmissive aperture. Neither of the Bartow et al. collimators produces planar beams.
The Bartow et al. patent describes avoidance of excessive concentration of X-rays at any particular spot on the subject skin or tissues by virtue of the discretely spaced small beams. The Bartow et al. patent also describes the rotational or translational movement of the emitting device to produce a cross-firing effect. The Bartow et al. patent does not, however, present any description of a tissue sparing effect at a microscopic level that might be attributable to the specific use of microbeams, positioned to produce just such an effect. Neither do Bartow et al. describe the use of parallel microbeams or the efficacy of the treatment of tumors using parallel microbeams without any converging or cross-firing effect.
U.S. Pat. No. 4,827,491 to Barish also describes accelerator beam collimators having at least one radiation transmission channel. The beams produced by the Barish collimator are generally convergent toward a predetermined target, and range in diameter from about 3 mm to about 4 mm. The Barish collimators are described as useful for the radiation treatment of intra-cranial tumors, but may be applied to treatment of other portions of the body. The Barish patent does not describe microbeams or their utility.
U.S. Pat. No. 2,624,013 to Marks describes a radiation barrier or collimator producing a plurality of relatively large, parallel, rectangular beams. The beams range in size from 0.25 inch to 1 inch on each side. The Marks patent describes the protection of skin by limiting the irradiation of the skin to areas between the beams, thereby helping to retain the skin's integrity. The internal efficacy of the radiation beams produced by the Marks invention is described as relying on recoil electrons to destroy internal tumors. The Marks patent does not describe converging beams or the use of microbeams.
U.S. Pat. No. 4,726,046 to Nunan describes a method and apparatus for generating a relatively small (0.5 mm .times.0.5 mm) radiation beam. The Nunan method employs a plan for producing an array of radiation exposures by sequentially scanning over a prescribed area and intermittently delivering radiation beams, but does not describe microbeams.
U.S. Pat. No. 2,139,966 to Loebell describes an X-ray apparatus designed to emit a plurality of convergent X-rays for the treatment of internal disorders. The Loebell apparatus employs several independently movable, X-ray emitting cathode/anode pairs, preferably arranged radially arranged to produce a converging array of beams. The Loebell apparatus is described as capable of eliminating the burning of skin area by the use of converging beams. The Loebell patent does not describe the use of microbeams.
U.S. Pat. No. 4,592,083 to O'Brien describes a rotating shutter for radiation beams. The high speed actuator for controlling the shutter eliminates transition time during which the X-ray dose is wasted. Also describing a beam shutter is U.S. Pat. No. 3,963,935 to Donnadille. This shutter is described as useful for limiting the entry of radiation beams from particle accelerators into irradiation rooms. Neither of these patents describes the use of either single or arrayed microbeams for radiation treatment of tumors.
U.S. Pat. No. 5,125,926 to Rudko et al. describes a system for synchronizing the pulsation of a surgical laser with the heartbeat of a patient undergoing laser heart surgery. The Rudko et al. patent does not describe the synchronization of radiation beams for cancer therapy. Rudko et al. also do not describe the use of the synchronization method with tissues other than heart tissue. Furthermore, Rudko et al. do not disclose the synchronization of radiation impulses with other physiomechanical rhythms.
Although other methods and processes are known for radiation therapy, none provides a method for performing radiation therapy while avoiding significant radiation-induced damage to tissues surrounding the target.
Accordingly, it is a purpose of the present invention to provide a method for treating cancerous tumors by using extremely small radiation microbeams increasing the precision and accuracy of radiation therapy.
It is also a purpose of the present invention to provide a method of using extremely small microbeams of radiation to unexpectedly produce effective radiation therapy.
It is a further purpose of the present invention to provide an improved method of radiation therapy unexpectedly capable of avoiding significant radiation-induced damage to non-target tissues.
Other purposes and advantages of the present invention will be more fully apparent from the ensuing disclosure and appended claims.